Histidine-rich glycoprotein (HRGP), a plasma protein with antiheparin and antifibrinolytic activity, has been associated with thrombophilia in three families. Therefore, it may promote hypercoagulability. The following objectives have been achieved in the laboratory: purification of HRGP, development of an enzyme-linked immunosorbent assay for its quantitation, and confirmation of its antiheparin activity. In addition, we have discovered that some individuals have a single isoform of HRGP, while others have two forms. Preliminary work indicates that the differences represent heterogeneity of the oligosaccharide chains of this glycoprotein. An ongoing project is the study of HRGP binding to proteins that contain a "kringle" structure, such as plasminogen. By identifying binding sites for HRGP, we hope to discover potential functions for this protein.